auxilins

Summary

Summary: A family of proteins that play a role as cofactors in the process of CLATHRIN recycling in cells.

Top Publications

  1. Lee D, Wu X, Eisenberg E, Greene L. Recruitment dynamics of GAK and auxilin to clathrin-coated pits during endocytosis. J Cell Sci. 2006;119:3502-12 pubmed
    ..Therefore, budding as well as synchronous recruitment of GAK might be required for irreversible clathrin uncoating...
  2. Heymann J, Iwasaki K, Yim Y, Cheng N, Belnap D, Greene L, et al. Visualization of the binding of Hsc70 ATPase to clathrin baskets: implications for an uncoating mechanism. J Biol Chem. 2005;280:7156-61 pubmed
    ..Three Hsc70s remain bound to the dissociated triskelion, close to its trimerization hub...
  3. Hagedorn E, Bayraktar J, Kandachar V, Bai T, Englert D, Chang H. Drosophila melanogaster auxilin regulates the internalization of Delta to control activity of the Notch signaling pathway. J Cell Biol. 2006;173:443-52 pubmed
    ..Furthermore, the fact that auxilin is required for Notch signaling suggests that ligand endocytosis in the signal-sending cells needs to proceed past coat disassembly to activate Notch. ..
  4. Lee D, Zhao X, Yim Y, Eisenberg E, Greene L. Essential role of cyclin-G-associated kinase (Auxilin-2) in developing and mature mice. Mol Biol Cell. 2008;19:2766-76 pubmed publisher
    ..We conclude that GAK deletion blocks development and causes lethality in adult animals by disrupting clathrin-mediated endocytosis. ..
  5. B cking T, Aguet F, Harrison S, Kirchhausen T. Single-molecule analysis of a molecular disassemblase reveals the mechanism of Hsc70-driven clathrin uncoating. Nat Struct Mol Biol. 2011;18:295-301 pubmed publisher
    ..Capture of conformational fluctuations may be a general mechanism for chaperone-driven disassembly of protein complexes...
  6. Guan R, Dai H, Han D, Harrison S, Kirchhausen T. Structure of the PTEN-like region of auxilin, a detector of clathrin-coated vesicle budding. Structure. 2010;18:1191-8 pubmed publisher
    ..We propose a specific geometry for auxilin association with a membrane bilayer and discuss implications of this model for the mechanism by which auxilin detects separation of a vesicle from its parent membrane. ..
  7. Massol R, Boll W, Griffin A, Kirchhausen T. A burst of auxilin recruitment determines the onset of clathrin-coated vesicle uncoating. Proc Natl Acad Sci U S A. 2006;103:10265-10270 pubmed publisher
  8. Yim Y, Sun T, Wu L, Raimondi A, De Camilli P, Eisenberg E, et al. Endocytosis and clathrin-uncoating defects at synapses of auxilin knockout mice. Proc Natl Acad Sci U S A. 2010;107:4412-7 pubmed publisher
    ..Collectively, our results demonstrate the specialized role of auxilin in the recycling of synaptic vesicles at synapses, but also show that its function can be partially compensated for by up-regulation of GAK. ..
  9. Bai T, Seebald J, Kim K, Ding H, Szeto D, Chang H. Disruption of zebrafish cyclin G-associated kinase (GAK) function impairs the expression of Notch-dependent genes during neurogenesis and causes defects in neuronal development. BMC Dev Biol. 2010;10:7 pubmed publisher
    ..In addition, our analysis suggests that zebrafish GAK has at least two functions during the development of neural tissues: an early Notch-dependent role in neuronal patterning and a late role in maintaining the survival of neural cells. ..

More Information

Publications57

  1. Fotin A, Cheng Y, Grigorieff N, Walz T, Harrison S, Kirchhausen T. Structure of an auxilin-bound clathrin coat and its implications for the mechanism of uncoating. Nature. 2004;432:649-53 pubmed
    ..Auxilin binding produces a local change in heavy-chain contacts, creating a detectable global distortion of the clathrin coat. We propose a mechanism by which local destabilization of the lattice promotes general uncoating. ..
  2. Jiang J, Prasad K, Lafer E, Sousa R. Structural basis of interdomain communication in the Hsc70 chaperone. Mol Cell. 2005;20:513-24 pubmed
    ..This analysis identifies interdomain interactions critical for chaperone function and supports an allosteric mechanism in which the interdomain linker invades and disrupts the interdomain interface when ATP binds. ..
  3. Hirst J, Sahlender D, Li S, Lubben N, Borner G, Robinson M. Auxilin depletion causes self-assembly of clathrin into membraneless cages in vivo. Traffic. 2008;9:1354-71 pubmed publisher
    ..study, we show that HeLa cells also express auxilin 1, previously thought to be neuron specific, and that both auxilins need to be depleted for inhibition of clathrin-mediated endocytosis and intracellular sorting...
  4. Xing Y, Böcking T, Wolf M, Grigorieff N, Kirchhausen T, Harrison S. Structure of clathrin coat with bound Hsc70 and auxilin: mechanism of Hsc70-facilitated disassembly. EMBO J. 2010;29:655-65 pubmed publisher
    ..Accumulation of the local strain thus imposed at multiple vertices can then lead to disassembly. ..
  5. Eun S, Lea K, Overstreet E, Stevens S, Lee J, Fischer J. Identification of genes that interact with Drosophila liquid facets. Genetics. 2007;175:1163-74 pubmed
    ..We describe the mutant alleles and mutant phenotypes of Rala and aux. We discuss the relevance of all of these genetic interactions to the function of Liquid facets in Notch signaling. ..
  6. Rothnie A, Clarke A, Kuzmic P, Cameron A, Smith C. A sequential mechanism for clathrin cage disassembly by 70-kDa heat-shock cognate protein (Hsc70) and auxilin. Proc Natl Acad Sci U S A. 2011;108:6927-32 pubmed publisher
  7. Ma Y, Greener T, Pacold M, Kaushal S, Greene L, Eisenberg E. Identification of domain required for catalytic activity of auxilin in supporting clathrin uncoating by Hsc70. J Biol Chem. 2002;277:49267-74 pubmed
    ..Therefore the C-terminal subdomain of the clathrin-binding domain of auxilin is required for auxilin to act catalytically, whereas the N-terminal subdomain strengthens auxilin-clathrin binding. ..
  8. Sever S, Skoch J, Newmyer S, Ramachandran R, Ko D, McKee M, et al. Physical and functional connection between auxilin and dynamin during endocytosis. EMBO J. 2006;25:4163-74 pubmed
    ..Together, our findings support the model that the GTP-bound conformation of dynamin tetramers stimulates formation of constricted coated pits at the plasma membrane by regulating the chaperone activity of hsc70/auxilin. ..
  9. Xiao J, Kim L, Graham T. Dissection of Swa2p/auxilin domain requirements for cochaperoning Hsp70 clathrin-uncoating activity in vivo. Mol Biol Cell. 2006;17:3281-90 pubmed
    ..These data suggest that the TPR and J-domains collaborate in a bipartite interaction with Hsp70 to regulate its activity in clathrin disassembly. ..
  10. Jiang J, Maes E, Taylor A, Wang L, Hinck A, Lafer E, et al. Structural basis of J cochaperone binding and regulation of Hsp70. Mol Cell. 2007;28:422-33 pubmed
  11. Kandachar V, Bai T, Chang H. The clathrin-binding motif and the J-domain of Drosophila Auxilin are essential for facilitating Notch ligand endocytosis. BMC Dev Biol. 2008;8:50 pubmed publisher
    ..Together, our observations argue that ligand endocytosis is critical for Notch signaling and auxilin participates in Notch signaling by facilitating ligand internalization. ..
  12. Gruschus J, Han C, Greener T, Ferretti J, Greene L, Eisenberg E. Structure of the functional fragment of auxilin required for catalytic uncoating of clathrin-coated vesicles. Biochemistry. 2004;43:3111-9 pubmed
  13. Toret C, Lee L, Sekiya Kawasaki M, Drubin D. Multiple pathways regulate endocytic coat disassembly in Saccharomyces cerevisiae for optimal downstream trafficking. Traffic. 2008;9:848-59 pubmed publisher
    ..In total, at least four separate processes are important for disassembly of endocytic complexes and efficient downstream trafficking of endocytic cargo. ..
  14. Lee D, Zhao X, Zhang F, Eisenberg E, Greene L. Depletion of GAK/auxilin 2 inhibits receptor-mediated endocytosis and recruitment of both clathrin and clathrin adaptors. J Cell Sci. 2005;118:4311-21 pubmed
  15. Korolchuk V, Banting G. CK2 and GAK/auxilin2 are major protein kinases in clathrin-coated vesicles. Traffic. 2002;3:428-39 pubmed
    ..In addition, we show that the 'stripped' CCV membranes that remain once the peripheral membrane proteins have been removed from CCVs inhibit CK2 but not GAK/auxilin2 activity. ..
  16. Young J, Barral J, Ulrich Hartl F. More than folding: localized functions of cytosolic chaperones. Trends Biochem Sci. 2003;28:541-7 pubmed
    ..Such flexibility is unique to the cytosolic Hsp70 and Hsp90 chaperone system. ..
  17. Eisenberg E, Greene L. Multiple roles of auxilin and hsc70 in clathrin-mediated endocytosis. Traffic. 2007;8:640-6 pubmed
  18. Eun S, Banks S, Fischer J. Auxilin is essential for Delta signaling. Development. 2008;135:1089-95 pubmed publisher
    ..We discuss these observations in the light of current models for the role of Epsin in ligand endocytosis and the role of ligand endocytosis in Notch signaling. ..
  19. Rapoport I, Boll W, Yu A, Böcking T, Kirchhausen T. A motif in the clathrin heavy chain required for the Hsc70/auxilin uncoating reaction. Mol Biol Cell. 2008;19:405-13 pubmed
    ..Thus, the QLMLT motif is required for Hsc-70-facilitated uncoating, consistent with the proposal that this sequence is a specific target of the chaperone...
  20. Newmyer S, Christensen A, Sever S. Auxilin-dynamin interactions link the uncoating ATPase chaperone machinery with vesicle formation. Dev Cell. 2003;4:929-40 pubmed
    ..The data suggest that dynamin regulates the action of molecular chaperones in vesicle budding during endocytosis...
  21. Smith C, Dafforn T, Kent H, Sims C, Khubchandani Aswani K, Zhang L, et al. Location of auxilin within a clathrin cage. J Mol Biol. 2004;336:461-71 pubmed
    ..The means by which auxilin could both aid clathrin coat assembly and displace clathrin from AP2 during uncoating is discussed. ..
  22. Ezaki B, Kiyohara H, Matsumoto H, Nakashima S. Overexpression of an auxilin-like gene (F9E10.5) can suppress Al uptake in roots of Arabidopsis. J Exp Bot. 2007;58:497-506 pubmed
    ..It was also suggested that a part of the Al influx occurred via endocytosis in root hair cells in Arabidopsis. The Al resistance in the #355-2 line may therefore be due to a lower Al uptake via endocytosis in the root hair region. ..
  23. Elsayed L, Drouet V, Usenko T, Mohammed I, Hamed A, Elseed M, et al. A Novel Nonsense Mutation in DNAJC6 Expands the Phenotype of Autosomal-Recessive Juvenile-Onset Parkinson's Disease. Ann Neurol. 2016;79:335-7 pubmed publisher
  24. Kalli A, Morgan G, Sansom M. Interactions of the auxilin-1 PTEN-like domain with model membranes result in nanoclustering of phosphatidyl inositol phosphates. Biophys J. 2013;105:137-45 pubmed publisher
    ..The interaction of membrane-bound auxilin-1 PTEN-like domain with negatively charged lipid headgroups results in nanoclustering of PIP2 molecules in the adjacent bilayer leaflet. ..
  25. Banks S, Cho B, Eun S, Lee J, Windler S, Xie X, et al. The functions of auxilin and Rab11 in Drosophila suggest that the fundamental role of ligand endocytosis in notch signaling cells is not recycling. PLoS ONE. 2011;6:e18259 pubmed publisher
    ..Taken together, these results argue strongly that at least in some cell types, the primary function of Notch ligand endocytosis is not for ligand recycling. ..
  26. Gruschus J, Greene L, Eisenberg E, Ferretti J. Experimentally biased model structure of the Hsc70/auxilin complex: substrate transfer and interdomain structural change. Protein Sci. 2004;13:2029-44 pubmed
    ..Interdomain electrostatic interactions also appear to play a role in stimulation of ATPase activity due to J-domain binding and substrate binding by Hsc70. ..
  27. Saffarian S, Cocucci E, Kirchhausen T. Distinct dynamics of endocytic clathrin-coated pits and coated plaques. PLoS Biol. 2009;7:e1000191 pubmed publisher
  28. Zhou X, Fabian L, Bayraktar J, Ding H, Brill J, Chang H. Auxilin is required for formation of Golgi-derived clathrin-coated vesicles during Drosophila spermatogenesis. Development. 2011;138:1111-20 pubmed publisher
    ..Our data suggest that Aux participates in forming these Golgi-derived clathrin-positive vesicles and that Aux, therefore, has a role in the secretory pathway. ..
  29. Morgan J, Jiang J, Oliphint P, Jin S, Gimenez L, Busch D, et al. A role for an Hsp70 nucleotide exchange factor in the regulation of synaptic vesicle endocytosis. J Neurosci. 2013;33:8009-21 pubmed publisher
    ..These observations indicate that the action of a NEF, most likely Hsp110, is normally required during SV trafficking to release clathrin from Hsc70 and make it available for additional rounds of endocytosis. ..
  30. Olgiati S, Quadri M, Mandemakers W, Bonifati V. Reply. Ann Neurol. 2016;79:337-8 pubmed publisher
  31. Suetsugu N, Kagawa T, Wada M. An auxilin-like J-domain protein, JAC1, regulates phototropin-mediated chloroplast movement in Arabidopsis. Plant Physiol. 2005;139:151-62 pubmed
    ..Together, these results suggest that JAC1 is an essential component of phototropin-mediated chloroplast movement. ..
  32. Jiang J, Taylor A, Prasad K, Ishikawa Brush Y, Hart P, Lafer E, et al. Structure-function analysis of the auxilin J-domain reveals an extended Hsc70 interaction interface. Biochemistry. 2003;42:5748-53 pubmed
    ..The latter loop extends the positively charged surface which forms the Hsc70 binding site, and is shown by directed mutagenesis and surface plasmon resonance to contain side chains important for binding to Hsc70. ..
  33. Jackson L, Kümmel D, Reinisch K, Owen D. Structures and mechanisms of vesicle coat components and multisubunit tethering complexes. Curr Opin Cell Biol. 2012;24:475-83 pubmed publisher
  34. Edvardson S, Cinnamon Y, Ta Shma A, Shaag A, Yim Y, Zenvirt S, et al. A deleterious mutation in DNAJC6 encoding the neuronal-specific clathrin-uncoating co-chaperone auxilin, is associated with juvenile parkinsonism. PLoS ONE. 2012;7:e36458 pubmed publisher
    ..The present report underscores the importance of the endocytic/lysosomal pathway in the pathogenesis of Parkinson disease and other forms of parkinsonism. ..
  35. Ichikawa S, Yamada N, Suetsugu N, Wada M, Kadota A. Red light, Phot1 and JAC1 modulate Phot2-dependent reorganization of chloroplast actin filaments and chloroplast avoidance movement. Plant Cell Physiol. 2011;52:1422-32 pubmed publisher
    ..Further, JAC1 is suggested to function in the biased cp-actin filament distribution by regulating their appearance and disappearance. ..
  36. Ding J, Segarra V, Chen S, Cai H, Lemmon S, Ferro Novick S. Auxilin facilitates membrane traffic in the early secretory pathway. Mol Biol Cell. 2016;27:127-36 pubmed publisher
    ..In the case of COPII vesicles, we link this delay to a defect in vesicle fusion. We propose that auxilin acts as a chaperone and/or uncoating factor for transport vesicles that act in the early secretory pathway. ..
  37. Augustine G, Morgan J, Villalba Galea C, Jin S, Prasad K, Lafer E. Clathrin and synaptic vesicle endocytosis: studies at the squid giant synapse. Biochem Soc Trans. 2006;34:68-72 pubmed
    ..Taken together, these results indicate that a clathrin-dependent pathway is the primary means of SV recycling at this synapse under physiological conditions. ..
  38. Scheele U, Alves J, Frank R, Duwel M, Kalthoff C, Ungewickell E. Molecular and functional characterization of clathrin- and AP-2-binding determinants within a disordered domain of auxilin. J Biol Chem. 2003;278:25357-68 pubmed
    ..Like AP180, auxilin also directly interacts with the ear domain of beta-adaptin. On the basis of our data, we propose a refined model for the uncoating mechanism of clathrin-coated vesicles. ..
  39. Montagnac G, de Forges H, Smythe E, Gueudry C, Romao M, Salamero J, et al. Decoupling of activation and effector binding underlies ARF6 priming of fast endocytic recycling. Curr Biol. 2011;21:574-9 pubmed publisher
    ..Our findings unravel a novel mechanism of separation of ARF6 activation and effector function, ensuring that fast recycling may be determined at the level of receptor incorporation into CCPs. ..
  40. Kodama Y, Suetsugu N, Kong S, Wada M. Two interacting coiled-coil proteins, WEB1 and PMI2, maintain the chloroplast photorelocation movement velocity in Arabidopsis. Proc Natl Acad Sci U S A. 2010;107:19591-6 pubmed publisher
    ..Our findings suggest that a cytosolic WEB1-PMI2 complex maintains the velocity of chloroplast photorelocation movement via cp-actin filament regulation. ..
  41. Scott H, Howarth J, Lee Y, Wong L, Bantounas I, Phylactou L, et al. MiR-3120 is a mirror microRNA that targets heat shock cognate protein 70 and auxilin messenger RNAs and regulates clathrin vesicle uncoating. J Biol Chem. 2012;287:14726-33 pubmed publisher
    ..Finally, mirror miRNAs are likely to represent a new group of miRNAs with complex roles in coordinating gene expression. ..
  42. Sever S, Skoch J, Bacskai B, Newmyer S. Assays and functional properties of auxilin-dynamin interactions. Methods Enzymol. 2005;404:570-85 pubmed
    ..Here we describe three different in vitro assays that monitor auxilin-dynamin interactions, as well as fluorescence lifetime imaging microscopy that identify direct interactions between dynamin and auxilin in cells. ..
  43. Young A, Stoilova McPhie S, Rothnie A, Vallis Y, Harvey Smith P, Ranson N, et al. Hsc70-induced changes in clathrin-auxilin cage structure suggest a role for clathrin light chains in cage disassembly. Traffic. 2013;14:987-96 pubmed publisher
    ..These data support a regulatory role for clathrin light chains in clathrin disassembly in addition to their established role in regulating clathrin assembly. ..
  44. Quadri M, Fang M, Picillo M, Olgiati S, Breedveld G, Graafland J, et al. Mutation in the SYNJ1 gene associated with autosomal recessive, early-onset Parkinsonism. Hum Mutat. 2013;34:1208-15 pubmed publisher
    ..Our data delineate a novel form of human Mendelian Parkinsonism, and provide further evidence for abnormal synaptic vesicle recycling as a central theme in the pathogenesis. ..
  45. Takano A, Suetsugu N, Wada M, Kohda D. Crystallographic and functional analyses of J-domain of JAC1 essential for chloroplast photorelocation movement in Arabidopsis thaliana. Plant Cell Physiol. 2010;51:1372-6 pubmed publisher
    ..These results suggest that the requirement of JAC1 in chloroplast photorelocation movement is attributable to the J-domain's cochaperone activity. ..
  46. Brodsky F. Cell biology: clathrin's Achilles' ankle. Nature. 2004;432:568-9 pubmed
  47. Krantz K, Puchalla J, Thapa R, Kobayashi C, Bisher M, Viehweg J, et al. Clathrin coat disassembly by the yeast Hsc70/Ssa1p and auxilin/Swa2p proteins observed by single-particle burst analysis spectroscopy. J Biol Chem. 2013;288:26721-30 pubmed publisher
  48. Shi Y, Yuan M, Chen J, Sun F, Pang Y. [Effects of helper protein P20 from Bacillus thuringiensis on Vip3A expression]. Wei Sheng Wu Xue Bao. 2006;46:85-9 pubmed
    ..Cell supernatants of two strains containing small amounts of secreted Vip3A were not toxic to the tested insect. It suggests that p20 can enhance the expression of Vip3A, but not improve its insecticidal toxicity remarkably. ..